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Abstract：
BACKGROUND: Filaggrin gene (FLG) expression, particularly in the skin, has been linked to the development of the skin barrier and is associated with eczema risk. However, knowledge as to whether FLG expression in umbilical cord blood (UCB) is associated with eczema development and prediction is lacking.
OBJECTIVE: This study sought to assess whether FLG expression in UCB associates with and predicts the development of eczema in infancy.
METHODS: Infants enrolled in a birth cohort study (n=94) were assessed for eczema at ages 3, 6, and 12 months. Five probes measuring FLG transcripts expression in UCB were available from genomewide gene expression profiling. FLG genetic variants R501X, 2282del4, and S3247X were genotyped. Associations were assessed using Poisson regression with robust variance estimation. Area under the curve (AUC), describing the discriminatory/predictive performance of fitted models, was estimated from logistic regression.
RESULTS: Increased level of FLG expression measured by probe A_24_P51322 was associated with reduced risk of eczema during the first year of life (RR=0.60, 95% CI: 0.38-0.95). In contrast, increased level of FLG antisense transcripts measured by probe A_21_P0014075 was associated with increased risk of eczema (RR=2.02, 95% CI: 1.10-3.72). In prediction models including FLG expression, FLG genetic variants, and sex, discrimination between children who will and will not develop eczema at 3 months of age was high (AUC: 0.91, 95% CI: 0.84-0.98).
CONCLUSIONS: This study demonstrated, for the first time, that FLG expression in UCB is associated with eczema development in infancy. Moreover, our analysis provided prediction models that were capable of discriminating, to a great extent, between those who will and will not develop eczema in infancy. Therefore, early identification of infants at increased risk of developing eczema is possible and such high-risk newborns may benefit from early stratification and intervention.
OBJECTIVE: This study sought to assess whether FLG expression in UCB associates with and predicts the development of eczema in infancy.
METHODS: Infants enrolled in a birth cohort study (n=94) were assessed for eczema at ages 3, 6, and 12 months. Five probes measuring FLG transcripts expression in UCB were available from genomewide gene expression profiling. FLG genetic variants R501X, 2282del4, and S3247X were genotyped. Associations were assessed using Poisson regression with robust variance estimation. Area under the curve (AUC), describing the discriminatory/predictive performance of fitted models, was estimated from logistic regression.
RESULTS: Increased level of FLG expression measured by probe A_24_P51322 was associated with reduced risk of eczema during the first year of life (RR=0.60, 95% CI: 0.38-0.95). In contrast, increased level of FLG antisense transcripts measured by probe A_21_P0014075 was associated with increased risk of eczema (RR=2.02, 95% CI: 1.10-3.72). In prediction models including FLG expression, FLG genetic variants, and sex, discrimination between children who will and will not develop eczema at 3 months of age was high (AUC: 0.91, 95% CI: 0.84-0.98).
CONCLUSIONS: This study demonstrated, for the first time, that FLG expression in UCB is associated with eczema development in infancy. Moreover, our analysis provided prediction models that were capable of discriminating, to a great extent, between those who will and will not develop eczema in infancy. Therefore, early identification of infants at increased risk of developing eczema is possible and such high-risk newborns may benefit from early stratification and intervention.
摘要：
背景：Filaggrin基因（FLG）表达，特别是在皮肤上，与皮肤屏障的发展有关，并与湿疹风险有关。然而,缺乏关于脐带血（UCB）中FLG表达是否与湿疹发展相关的知识和预测。
目的：本研究旨在评估UCB中FLG的表达是否与婴儿期湿疹的发展相关，并对其进行预测。
方法：纳入出生队列研究的婴儿（n=94）在3、6和12个月时进行湿疹评估。可从全基因组基因表达谱分析获得测量UCB中FLG转录本表达的五个探针。FLG遗传变异R501X,对2282del4和S3247X进行基因分型。使用具有稳健方差估计的泊松回归评估关联。曲线下面积（AUC），描述拟合模型的判别/预测性能，是从逻辑回归估计的。
结果：通过探针A_24_P51322测量的FLG表达水平升高与生命第一年湿疹风险降低相关（RR=0.60，95％CI：0.38-0.95）。相比之下,通过探针A_21_P0014075测量的FLG反义转录本水平升高与湿疹风险增加相关(RR=2.02,95%CI:1.10-3.72)。在包括FLG表达的预测模型中，FLG遗传变异,和性,在3月龄时将患和不患湿疹的儿童之间的歧视很高(AUC:0.91,95%CI:0.84-0.98).
结论：这项研究表明，第一次,UCB中FLG的表达与婴儿期湿疹的发展有关。此外，我们的分析提供了能够区分的预测模型，在很大程度上,在婴儿期会和不会发展湿疹的人之间。因此,早期发现患湿疹风险增加的婴儿是可能的,此类高危新生儿可从早期分层和干预中获益.
目的：本研究旨在评估UCB中FLG的表达是否与婴儿期湿疹的发展相关，并对其进行预测。
方法：纳入出生队列研究的婴儿（n=94）在3、6和12个月时进行湿疹评估。可从全基因组基因表达谱分析获得测量UCB中FLG转录本表达的五个探针。FLG遗传变异R501X,对2282del4和S3247X进行基因分型。使用具有稳健方差估计的泊松回归评估关联。曲线下面积（AUC），描述拟合模型的判别/预测性能，是从逻辑回归估计的。
结果：通过探针A_24_P51322测量的FLG表达水平升高与生命第一年湿疹风险降低相关（RR=0.60，95％CI：0.38-0.95）。相比之下,通过探针A_21_P0014075测量的FLG反义转录本水平升高与湿疹风险增加相关(RR=2.02,95%CI:1.10-3.72)。在包括FLG表达的预测模型中，FLG遗传变异,和性,在3月龄时将患和不患湿疹的儿童之间的歧视很高(AUC:0.91,95%CI:0.84-0.98).
结论：这项研究表明，第一次,UCB中FLG的表达与婴儿期湿疹的发展有关。此外，我们的分析提供了能够区分的预测模型，在很大程度上,在婴儿期会和不会发展湿疹的人之间。因此,早期发现患湿疹风险增加的婴儿是可能的,此类高危新生儿可从早期分层和干预中获益.
